Relationships between duplex findings and quality of life in long-term follow-up of patients treated for chronic venous disease

Abstract

Objective

Relationships between duplex findings and data on health-related quality of life (QoL) to assess long-term results of treatment of varicose veins and chronic venous insufficiency (CVI) are not well known. The goal of this review was to correlate duplex findings and QoL assessments in clinical studies with long-term follow-up.

Methods

A review of the English language literature on PUBMED revealed 17 clinical studies, including 9 randomized controlled trials (RCTs), 6 prospective, and 2 retrospective studies that included patients with at least 5-year follow-up after endovenous laser ablation (EVLA), radiofrequency ablation (RFA), ultrasound-guided foam sclerotherapy (UGFS), and traditional superficial venous surgery.

Results

At 5 years, great saphenous vein (GSV) occlusion rate on duplex ultrasound ranged from 66% to 82% for EVLA, from 62% to 92% for RFA, from 41% to 58% for UGFS and from 54% to 85% for surgery. Freedom from GSV reflux rates were 82% and 84%, respectively for EVLA and surgery, and ranged between 84% and 95% for RFA. Significant improvements were observed in several domains of generic QoL and in most domains of venous disease-specific QoL, irrespective of the treatment. In at least one RCT, CIVIQ scores correlated well with abnormal duplex findings in patients who underwent treatment with UGFS. In another RCT, long-term AVVQ was significantly better after surgery as compared with UGFS similar to results of duplex findings.

Conclusions

Analysis of the available literature confirmed that all four techniques were effective in the abolishment of reflux or obliteration of the GSV. Moreover, well-designed RCTs with large sample size are needed to produce robust long-term data on clinical outcome after treatment of varicose veins and CVI and to better understand the relationships between duplex-derived data and QoL assessments.

Keywords

Varicose veins endovenous thermal ablation foam sclerotherapy duplex ultrasound quality of life assessment

Introduction

Progress in minimally invasive techniques to treat varicose veins and chronic venous insufficiency (CVI) in the last two decades has been tremendous. Endovenous laser ablation (EVLA), radiofrequency ablation (RFA), and ultrasound-guided foam sclerotherapy (UGFS) are less invasive techniques than traditional surgery and have quicker recovery time. Mid-term results comparing any of these techniques have failed to show superiority of any of them over another. Current guidelines recommend endovenous thermal ablations (EVTA) as the treatment of choice for a refluxing saphenous vein.^1,2

The aim of this review was to investigate the relationships between results of duplex evaluations and data on quality of life (QoL) in randomized controlled trials (RCTs), prospective observational studies, and retrospective studies with long-term follow-up of patients who underwent interventions for varicose veins or CVI.

Methods

We searched English language articles in Pubmed with no limit for publication dates and the last search was on 3 November 2015. Search terms were: varicose veins, chronic venous insufficiency, chronic venous disease, endovenous, endovenous laser, endovenous laser ablation, EVLA, EVLT, radiofrequency, RFA, sclerotherapy, foam sclerotherapy, ultrasound-guided foam sclerotherapy, UGFS, venous surgery, saphenous vein ablation, high ligation, sapheno-femoral ligation, stripping varicose veins, duplex, duplex ultrasound, reflux, obliteration, recurrence, quality of life, quality of life questionnaire, SF-36, Euroqol, VEINES-QoL, CIVIQ, AVVQ, AVVSS, CXVUQ, long-term, long-term outcome, 5-year, 5 years. The inclusion criteria for eligible articles included in this review were as follows: RCTs, prospective or retrospective observational studies of EVLA, RFA, UGFS, or traditional venous surgery for the treatment of chronic venous disease, with at least 5-year follow-up results in terms of duplex findings and/or QoL.

We identified 17 articles for our review, including 9 RCTs, 6 prospective, and 2 retrospective studies. Nine of these studies were performed in single institutions while 8 studies were multi-institutional studies. Published data on physical examination, preoperative and postoperative duplex scanning, physician and patient reported outcome evaluations were reviewed using criteria for abnormal findings as suggested by society guidelines.^1–3 The cutoff value for reflux due to clinically significant valvular incompetence as recorded by duplex scanning was 0.5 s in the saphenous, tibial, deep femoral, and perforating veins, and 1.0 second in the femoral and popliteal veins.¹ The definition of “pathologic” perforating veins included those with outward flow of ≥ 0.5 s, with a diameter of ≥ 3.5 mm, located beneath a healed or open venous ulcer (CEAP class C₅–C₆).¹

QoL assessment was reviewed as performed with generic (health-related) and venous disease-specific QoL instruments. Generic QoL instruments included the Short Form 36-Item Health Survey (SF-36) and the Euroqol (EQ-5D).^1,2 SF-36 included one multi-item scale that assesses eight health concepts including limitations in physical activities because of health problems (PF), limitations in social activities because of physical or emotional problems (SF), limitations in usual role activities because of physical health problems (RP), bodily pain, general mental health (MH), limitations in usual role activities because of emotional problems (RE), vitality (VT), and general health perception (GH). Venous disease-specific QoL instruments included the Venous Insufficiency Epidemiologic and Economic Study of Quality-of-Life (VEINES-QoL/Sym) questionnaire scale, the Chronic Venous Insufficiency Questionnaire (CIVIQ), the Aberdeen Varicose Vein Questionnaire (AVVQ) or the Aberdeen Varicose Vein Severity Score (AVVSS), and the Charing Cross Venous Ulceration Questionnaire (CXVUQ).^1,2

Results

Studies with both duplex findings and QoL assessments

Results from randomized controlled trials

The Dutch EVLA versus cryostripping RCT⁴ In this single-center RCT, 120 patients with primary symptomatic varicose veins were randomized to EVLA (n = 60) or cryostripping (n = 60). All limbs were CEAP (Clinical Etiologic Anatomic Pathophysiologic) clinical class C₂, and all had saphenofemoral junction (SFJ) incompetence and great saphenous vein (GSV) reflux from the groin to below the knee. Diode laser (600 µm, 810 nm; Diomed, Andover, MA, USA) was used for EVLA; high ligation along with cryostripping of the GSV using a cryostripping unit (Erbe, Tubingen, Germany) was performed in the cryostripping patient group. Incompetent GSV was defined as an open section of the treated segment over 5.0 cm in length, with reflux exceeding 0.5 s on duplex; incompetent tributaries were defined as bidirectional flow that had not been observed before; neovascularization was defined as serpentine tributaries arising from the ligated SFJ. Forty-four patients (37%) were lost to follow-up, leaving 41 patients (68%) for analysis in the EVLA group and 35 (58%) in the cryostripping group. Duplex findings. Freedom from incompetence and from neovascularization rates at 5 years were not significantly different between EVLA and the cryostripping group (p = 0.25), 62% after EVLA and 51% after cryostripping. However, GSV incompetence was more common after EVLA than after cryostripping (7% vs. 0%, p = 0.04); so was tributary incompetence (15% vs. 0%, p = 0.002). Neovascularization was more frequent after cryostripping than after EVLA (28% vs. 0%, p < 0.001) at 5 years. QoL assessment. The AVVSS values improved significantly after both treatments and were maintained for 5 years. The scores decreased from 15.8 at preoperative baseline to 5.4 at 5 years for EVLA and from 13.6 to 3.8 for cryostripping, reaching no statistical significance between groups at the end of follow-up (p = 0.72). Comments. Duplex evaluation showed no statistical difference in composite incompetence and neovascularization; neovascularization on duplex, however, was less common and incompetent tributaries were more frequent after EVLA than after cryostripping. Both EVLA and cryostripping significantly improved disease-specific QoL in terms of AVVSS, and the effect lasted at least 5 years with no statistical significance between the groups. Abnormal duplex findings in terms of GSV or tributary incompetence as well as neovascularization did not affect long-term QoL.

The Danish EVLA versus surgery RCT⁵ In this two-center RCT, 137 lower extremities with GSV incompetence (CEAP C_2-4E_pA_sP_r) in 121 patients were randomized to EVLA (n = 69) or conventional venous surgery treated with high ligation, division of all tributaries, and stripping of the GSV to the below-knee level (HLS, n = 68). EVLA was performed using 980-nm diode laser at 12 W pulsed mode (Ceralas D 980; Biolitec, Bonn, Germany), the GSV was treated from the below-knee level, or at the lowest point of reflux on the thigh, till up to 1–2 cm below the SFJ. Concomitant mini-phlebectomies were performed in both groups. The duplex study endpoint was refluxing GSV segment ≥ 5.0 cm. Nineteen patients (20 limbs) in HLS group and 21 patients (23 limbs) in EVLA group were available for analysis at 5 years. Duplex findings. There was no significant difference between EVLA and surgery groups in terms of GSV reflux, the rates were 18% and 10%, respectively at 5 years (p = 0.21). There were more incompetent refluxing anterior accessory great saphenous veins (AAGSVs) after EVLA (24% vs. 13%, p = 0.31) and more incompetent thigh perforators after surgery (33% vs. 20%, p = 0.37), but the differences were not statistically significant. QoL assessment. SF-36 QoL improved in some domains at 5 years compared with preoperative baseline values, which included vitality, mental health and physical function in both treatment groups (p < 0.05). The AVVSS also improved significantly in both groups, which started at 3 months after the procedure (p < 0.001). The scores decreased from 18 at preoperative baseline to 3.0 at 5 years for EVLA and from 16 to 3.6 for HLS patients. Both SF-36 and AVVSS showed no statistical significance between treatment groups. Comments. Five-year follow-up did not show significant difference between EVLA and surgery in terms of duplex-derived GSV reflux and QoL. EVLA seems to be a valid alternative to open surgery with long-term benefit in patients with varicose veins. Both EVLA and surgery significantly improved several domains of SF-36 and AVVSS and the improvements persisted throughout the 5 years. Duplex findings correlated with good clinical outcome as measured by QoL.

The German EVLA versus surgery RCT⁶ Patients with GSV incompetence (C₂–C₆) were included in this two-center RCT, 185 were treated with EVLA, 161 with high ligation and stripping of the GSV (HLS). Duplex recurrence was defined as re-appearance of reflux in the groin (>0.5 s) detected in vessels ≥2.0 mm connected with the common femoral vein, and in case of EVLA, reflux had to be identified at least 2.0 cm distal from the SFJ. Duplex findings. Two hundred and eighty-one limbs (81%; EVLA: 82%, HLS: 80%) were evaluated at a median follow-up of 60.4 months for EVLA and 60.7 months for HLS. Duplex-detected SFJ reflux was significantly more common after EVLA than after HLS (p < 0.001), the rates were 28% and 5%, respectively at 5 years. In the EVLA group, of 42 limbs with SFJ reflux, GSV recanalization from the SFJ was observed in 26 limbs (62%), and in 20 limbs, incompetent groin tributaries were seen; AAGSV reflux accounted for 48%. Clinical recurrence occurred in 27 (64%) of the duplex-detected recurrences at the SFJ, and a reoperation was required in 6 limbs. The mean reflux length was 11 cm (range: 2.5–40 cm). In the HLS group, of 6 limbs with duplex-detected SFJ reflux, neovascularization was seen in 4 cases and veins developing from a residual stump in 2 cases; 2 cases of neovascularization had minor clinical recurrence not requiring reoperation. QoL assessment. CIVIQ-2 was used for QoL assessment. Significant improvements were observed in overall score, pain, physical, psychological, and social function, which started at postoperative month 3 and were maintained at least 5 years, reaching no significant differences between treatment groups. In addition, overall patient satisfaction was also comparative at 5 years (EVLA: 1.28, HLS: 1.39, p = 0.08). Comments. Both EVLA and HLS were comparably effective concerning varicose vein recurrence, QoL and patient satisfaction at 5 years. However, HLS was superior to EVLA in terms of long-term duplex-detected recurrence. Differences in duplex findings were not reflected in the QoL data.

The Austrian EVLA with high ligation of the GSV versus surgery RCT⁷ EVLA plus high ligation of the GSV (HL + EVLA, 810 nm, 12 W) was compared with high ligation and stripping of the GSV (HLS) in this two-center RCT. One-hundred patients with C₂ to C₄ disease participated in the study, 96 (96%) were included in the per protocol analysis, 72 (75%) completed the 5-year follow-up (HLS: 40, 83%; HL + EVLA: 32, 68%). Duplex findings. There was no statistical difference in recurrences on clinical examination and duplex ultrasound between treatment groups (HLS: 55%, HL + EVLA: 40%, p = 0.22). Rates of reopened or residual incompetent GSV were similar, 24% for HLS and 40% for HL + EVLA (p = 0.14). The entire GSV was reopened in 10% of the EVLA patients. Freedom from varicosity was significantly higher after HLS as compared with that after HL + EVLA (67% vs. 43%, p = 0.049), but incompetent perforators were more common after HLS (21% vs. 0%, p = 0.007). QoL assessment. There were significant improvements after treatment compared with preoperative values for both groups in CIVIQ-2 (HL + EVLA: 75 vs. 93, HLS: 82 vs. 94, p < 0.001), but there was no statistical significance shown in overall scores and subscores between treatment groups. In addition, patient satisfaction with the overall results was also similar irrespective of the treatment. Comments. Favorable clinical results, venous disease-specific QoL and high patient satisfaction were similarly achieved following HLS or HL + EVLA. However, varicose vein recurrence remains a concern, and in this study, it was more frequent after HL + EVLA, but incompetent perforators were more common after HLS. Similar to duplex findings, QoL data showed improvements and there was no difference between the groups.

The UK UGFS plus high ligation versus surgery RCT⁸ Patients with primary varicose veins secondary to GSV incompetence (C₂–C₆) were included in this two-center RCT, 39 were treated with high ligation of the GSV plus UGFS (HL + UGFS) and 43 with high ligation and stripping of the GSV in combination with phlebectomies (HLS). 3% sodium tetradecyl sulfate (STS; STD Pharmaceuticals, Hereford, UK) was used as the sclerosing agent. Median follow-up was 5 years. Duplex findings. Above-knee obliteration of GSV without reflux was seen in 54% (14/26) of the HLS patients and in 58% (19/33) of the HL + UGFS patients (58%) (p = 0.19). For below-knee obliteration of GSV without reflux, it was 39% (10/26) for HLS and 24% (8/33) for HL + UGFS (p = 0.34). QoL assessment. SF-36 mental summary scores over 3 years deteriorated after HLS (p = 0.04), but the physical scores did not change between groups (HLS: p = 0.36; HL + UGFS: p = 0.89), neither did the mental scores for HL + UGFS (p = 0.29). The AVVQ improved for both treatment groups and significantly better AVVQ scores for HLS compared with HL + UGFS were observed at 5 years (p = 0.02). Comments. The treatment was equally effective in the surgical and UGFS groups with respect to duplex-based obliteration of GSV and SF-36 physical component scores. The AVVQ was significantly better in the surgical group as compared with UGFS at 5 years. Favorable duplex findings did not always correlate with some QoL data.

The Dutch EVLA versus UGFS versus surgery RCT⁹ Patients with SFJ reflux and above-knee GSV reflux with GSV diameter of at least 5.0 mm in mid-thigh (C₁–C₅) were included in this multicenter, three-arm RCT. The treatment groups were high ligation and stripping of the above-knee GSV with concomitant phlebectomies of varicose tributaries (HLS: n = 69), EVLA (n = 78, 940 nm, 10 W), and UGFS of the GSV using 3% polidocanol (n = 77). Duplex scanning was performed in 33% of the participants at 5 years (HLS: 36%, EVLA: 40%, UGFS: 23%). Duplex findings. Rates of obliteration or absence of the GSV were 85% for HLS, 77% for EVLA and 23% for UGFS at 5 years (p < 0.001). In addition, patients treated with HLS or EVLA were four times more likely to have persisting obliteration of the above-knee GSV than patients with UGFS (UGFS/HLS restricted mean survival time (RMST) ratio: 0.6, 0.5–0.7; UGFS/EVLA RMST ratio: 0.6, 95% CI: 0.5–0.8), rates were 85%, 82%, and 41%, respectively at 5 years. Persistent or recurrent reflux at the SFJ was more common after UGFS and EVLA than after HLS at 5 years (31% and 22% vs. 13%, p = 0.003), but reaching no statistical significance when compared EVLA with UGFS (p = 0.24). Neovascularization occurred in 44% of lower limbs after HLS, in 11% after EVLA and in 3% after UGFS; HLS was more likely to develop neovascularization in smaller veins (<4.0 mm) which were limited to the groin area than those treated by EVLA (OR 12.9, 95% CI: 2.8–59) or UGFS (OR 1.5, 95% CI: 1.2–1.8), whereas neovascularization in larger tortuous refluxing veins (≥ 4.0 mm) was similar following HLS and EVLA (p = 0.61). QoL assessment. EQ-5D scores improved equally in all treatment groups. UGFS was associated with inferior CIVIQ scores when compared with EVLA (0.98 increase vs. −0.44 decrease per year, p = 0.01), and the CIVIQ scores for HLS patients did not differ from those for EVLA and UGFS patients (0.44 increase per year, 95% CI: −0.41 to 1.29). Comments. The study demonstrated that conventional surgery and EVLA are more effective than UGFS in the treatment of GSV reflux. EVLA provides better disease-specific patient-reported outcomes than UGFS 5 years after intervention, but similar to those after conventional surgery. Inferior CIVIQ score in UGFS patients correlated well with duplex findings confirming low late occlusion rates after UGFS.

The UK 12 W versus 14 W EVLT RCT¹⁰ Patients with primary symptomatic, unilateral varicose veins secondary to SFJ incompetence and GSV reflux (C₂, C₄–C₅) were randomized to EVLA (810 nm, Diomed/Angiodynamics, Cambridge, UK) at 12 W (intermittent laser withdrawal, n = 38) and 14 W group (continuous laser withdrawal, n = 38) in this single-center RCT. Different from other studies, venous incompetence in this study was defined as duplex-detected reflux exceeding 1.0 second post distal augmentation maneuvers. Duplex findings. Rate of abolition of SFJ reflux 5 years after EVLA was superior for the 14 W as compared with 12 W group (94%, 29/31 vs. 66%, 19/29, p = 0.02). In the 12 W group, of 10 limbs with SFJ incompetence, reflux into AAGSV was seen in 5, into groin tributaries in 3 and reopening of the GSV was seen in 2 which resulted in clinical recurrence. In the 14 W group, of 2 limbs with SFJ incompetence, reflux into AAGSV and groin tributaries was seen in one limb each. In 13 legs with GSV reflux, 12 developed clinical recurrence. Abolition of GSV reflux was similar between 12 W and 14 W power settings (93%, 27/29 vs. 100%, 31/31, p = 0.27). QoL assessment. Five-year follow-up showed that 6 of the 8 domains in SF-36, including physical function, role-physical, bodily pain, general health, vitality, and mental health, p < 0.05) were significantly improved in the 14 W group, when compared to only bodily pain score (p = 0.001) in the 12 W group. The EQ-5D scores significantly improved at 3 months when compared to the baseline values in both groups (p = 0.001) and were maintained up to 5 years (p < 0.001). So did the AVVQ scores. There were no significant differences between the two power setting groups in SF-36, EQ-5D or AVVQ scores. Patients treated with 12 W reported significantly lower satisfaction with the cosmetic outcome at 5 years (p = 0.047); however, satisfaction with EVLA treatment was equally high in both groups with no significant difference (p = 0.07). Comments. Late outcome following EVLA was superior for the 14 W continuous power settings in terms of abolition of SFJ reflux based on duplex evidence, although both 12 W and 14 W treatments significantly improved generic and venous disease-specific QoL, with no statistical significance between treatment groups. There was some correlation between better duplex findings and improved SF-36 scores in the 14 W group.

Results from prospective observational studies

The Brazilian venous surgery prospective study¹¹ One study from Brazil reported long-term results from duplex exams as well as QoL after conventional venous surgery. In this study, 63 lower limbs with primary varicose veins secondary to GSV reflux (C₂–C₆) were treated with ankle-to-groin GSV stripping; simultaneous surgeries included phlebectomy in 55 and ligation of perforators in 8 patients. Patients with deep venous reflux were excluded from the study. Mean follow-up was 78 months. Duplex findings. Of 22 limbs examined by duplex, reflux was seen in 27% of the superficial, 14% of the deep venous systems, and 18% of the perforators. QoL assessment. Five-year results of patients undergoing varicose vein stripping showed that the overall CIVIQ scores as well as subscores of pain, physical, social, and psychological domains were significantly improved as compared with preoperative baseline values. Comments. In this small sample size prospective study with only 15 of 39 patients followed for 5 years, duplex findings were not detailed enough to draw major conclusions. Improvements in disease-specific QoL were seen after operation and were maintained at least 5 years.

Studies with duplex findings without QoL assessment

Results from RCTs

The German EVLA versus EVLA with high ligation versus surgery RCT¹² In this multicenter, three-arm RCT, 449 patients with primary varicose veins secondary to GSV reflux (Hach classification II–IV) were randomized to high ligation and stripping of GSV (HLS: n = 159), EVLA (n = 142; 980 nm, 30 W, Biolitec, Jena, Germany) and EVLA with high ligation of the GSV (HL + EVLA: n = 148). Median follow-up was 4.0 years; follow-up rate was 36% at 5 years and 31% at 6 years. Duplex findings. Reflux from SFJ into the GSV was significantly more frequent after EVLA (5-year HLS vs. EVLA: 9% vs. 40%, p = 0.005; HL + EVLA vs. EVLA: 13% vs. 40%, p = 0.008; 6-year HLS vs. EVLA: 12% vs. 45%, p = 0.01; HL + EVLA vs. EVLA: 7% vs. 45%, p < 0.001). In addition, reflux from SFJ into side branches was also more frequent after EVLA (5-year HLS vs. EVLA: 4% vs. 32%, p = 0.002; HL + EVLA vs. EVLA: 5% vs. 32%, p = 0.004; 6-year HLS vs. EVLA: 3% vs. 22%, p = 0.06; HL + EVLA vs. EVLA: 2% vs. 22%, p = 0.01). However, there were no significant differences among three treatment groups with regard to clinical recurrence (HLS vs. EVLA: p = 0.55; HLS vs. HL + EVLA: p = 0.23; HL + EVLA vs. EVLA: p = 0.08). Comments. Clinical recurrence were comparable among three treatment groups; however, duplex-detected SFJ reflux into the GSV and side branches were more common after EVLA. In this study, duplex findings did not correlate well with clinical outcome.

Results from prospective observational studies

The Swedish venous surgery prospective study¹³ One-hundred lower limbs (C₀–C₆) in 89 patients treated with primary SFJ ligation and stripping of the GSV were re-examined 6 to 10 years after primary operation in a single center. Varicose veins were present in 86 lower limbs. Duplex findings. Duplex-detected incompetent veins in the groin were shown in 57 limbs, including 50 in the former SFJ and 4 from the femoral vein in the vicinity of the SFJ. Comments. The authors concluded that recurrence of varicose veins after SFJ ligation is common. Duplex had good correlation with recurrence, clinical findings, symptoms, results of varicographies, and intraoperative findings during reoperation. Abnormal duplex findings, however, do not always require reinterventions.

The Swedish venous surgery prospective study¹⁴ This single-center study of an experienced venous surgeon included 104 lower limbs (C₃–C₄) following combined superficial venous surgery and subfascial endoscopic perforator surgery (SEPS); 71 limbs (68% of original study cohort) were available for final duplex examinations. Median follow-up was 12 years. Duplex findings. Incompetent perforators were seen in 25% (18/71) of the limbs. Duplex-detected groin recurrence was noted in 45% (23/51) of the limbs following groin surgery, 78% (18/23) were neovascularization. In addition, groin recurrence was also seen in 38% (14/37) of limbs with primary GSV surgery. Of 14 limbs with previously unknown deep vein incompetence (20%, 14/71), 6 had axial reflux. Comments. Clinical outcome was durable after venous surgery. Despite a fair number of duplex-detected recurrences, clinical relevance was low in this study. Groin neovascularization developed in less than half of the legs but it did not appear to affect patient satisfaction and was seldom a reason for reintervention.

The French RFA registry¹⁵ This multicenter prospective study included 1222 lower limbs in 1006 patients with duplex-confirmed superficial venous insufficiency (C₀–C₆). Mean age was 47 years, 78% were females. Above-knee GSVs were treated with RFA (VNUS Medical Technologies, Inc., San Jose, CA, USA) in 89%, below-knee GSVs in 1.2%, groin-to-ankle GSVs in 4.1%, small saphenous veins (SSVs) in 4.3%, and accessory saphenous veins in 1.3% of the limbs. Duplex findings. Five-year vein occlusion rate was 87%, freedom from reflux rate was 84%. Clinical symptom improvement was seen in 80% of limbs with anatomical failures, which was defined as failure identified by duplex ultrasound. Comments. This study suggested that duplex-derived anatomical failures due to recanalized veins and groin reflux were risk factors for increased recurrent varicose veins.

The European prospective study of RFA¹⁶ This recently published multicenter study included 295 GSVs in 225 patients, treated by RFA (120°C, 20-s heating cycles, Venefit™, Covidien, Mansfield, MA, USA). Complete occlusion was defined as absence of any reflux along the treated GSV up to 3.0 cm below the SFJ. Compliance with the duplex follow-up was 80% at 5 years. Duplex findings. The rate of GSV occlusion was 92% and freedom from reflux rate was 95% at 5 years. Of 15 GSVs with reflux, only three showed full recanalization of the GSV at 1 week, 6 months, and 3 years. Of 12 GSVs with partial recanalization, reflux originated at the SFJ was seen in 10, and only 6 patients were symptomatic. Comments. RFA proved to be an efficient endovenous treatment for incompetent GSVs in terms of occlusion and abolition of reflux in > 90% of the patients at 5 years. Duplex findings in general are more sensitive than clinical recurrence and only a portion of patients with abnormal duplex findings required re-treatment.

Results from retrospective studies

The Switzerland venous surgery study¹⁷ This retrospective study investigated 136 limbs in 91 patients treated previously with high ligation, stripping and a combination of other techniques to prevent recurrence, including stump coagulation, closure of the cribriform fascia and ligation of stripping of accessory saphenous veins. Smaller vessels with a diameter ≤ 3.0 mm without reflux were classified as nonrelevant, whereas relevant neovascularization was defined as a refluxing vein with diameter > 3.0 mm on duplex imaging. Duplex findings. The mean duplex follow-up was 10.7 years, nonrelevant neovascularizations were found in 1.5% of the treated limbs and there were no clinically relevant varicosities from the groin. Comments. The authors suggested that combined surgeries such as stump coagulation and suture of the fossa ovalis can reduce neovascularization and recurrent varicosities. Good duplex findings correlated with good late clinical outcomes.

The US EVLA with 810 nm diode versus EVLA with 1320 nm Nd:YAG versus RFA study¹⁸ This single-center retrospective three-arm study from the Maryland Laser Skin and Vein Institute included 934 lower limbs with incompetent GSVs (85%) or SSVs (15%). Patients were treated with EVLA with 810 nm diode (n = 34, 3.6%), with EVLA with 1320 nm Nd:YAG (n = 502, 54%) or with RFA (n = 398, 43%). Duplex findings. GSV reflux was defined as reflux > 1.0 s. There were significant differences in terms of complete obliteration of the treated veins among the three systems (p < 0.001), with the highest rate in 1320 nm Nd:YAG laser group as compared with the RF and 810 nm EVLT throughout their follow-up periods, 85%, 62%, and 66%, respectively at 5 years, and rates of recanalization were 6.8%, 28%, and 27%, respectively. Comments. Long-term efficacy was achieved in all groups but complete ablation varied significantly and EVLT with 1320 nm Nd:YAG laser provided the highest rate of GSV ablation. In this study, duplex scan at 8-year follow-up confirmed durable occlusion rates after EVTAs. Table 1 summarizes results of duplex findings in the literature.

Table 1.

Duplex findings at 5 years after interventions to treat chronic venous disease.

Author, year	Study period	Total limbs/ patients treated (N)	Treatment option	Limbs treated per treatment (n)	5-year duplex findings
Author, year	Study period	Total limbs/ patients treated (N)	Treatment option	Limbs treated per treatment (n)	GSV reflux (%)	p-Value	SFJ reflux (%)	p-Value	Others
RCTs
Disselhoff et al., 2011⁴	2003–2005	120/120	EVLA: cryostripping	60:60	7 vs 0	0.04	–	–	Duplex-derived incompetence and neovascularization: 38% vs 49%, p = 0.25 Tributary incompetence: 15% vs 0%, p = 0.002
Kalodiki et al., 2012⁸	–	82/73	HL + UGFS : HLS	39:43	–	–	–	–	Above-knee GSV reflux: 40% vs 35%, p = 0.19 Below-knee GSV reflux: 42% vs 35%, p = 0.34
Rasmussen et al., 2013⁵	–	137/121	EVLA : HLS	69:68	18 vs 10	0.21	–	–	Reflux into the GSV: 12% vs 8%, p = 0.66 Reflux into the AAGSV: 24% vs 13%, p = 0.31 Reflux into the groin: 8% vs 4%, p = 0.57 Reflux into the perforators: 20% vs 33%, p = 0.37
Rass et al., 2015⁶	2004–2007	346/346	EVLA : HLS	185:161 152:129^a	–	–	28 vs 5	<.001
Kalteis et al., 2015⁷	2004–2006	99/99	HL + EVLA : HLS	49:5032:40 ^a	–	–	–	–	Reopened/residual incompetent GSV: 40% vs 24%, p = 0.15 Incompetent perforators: 0% vs 21%, p = 0.007
Flessenkamper et al., 2014^1 2	2005–2009	449/449	EVLA : HL + EVLA : HLS	142:148:159 45:63:53^a	40 vs 13 vs 9^b	<0.05	–	–	Reflux from SFJ into side branches: 32% vs 5% vs 4%, EVLA vs HL + EVLA: p = 0.004, EVLA vs HLS: p = 0.002
van der Velden et al., 2015⁹	2007–2009	224/224	EVLA : UGFS : HLS	78:77:69 70:64:65^a	–	–	22 vs 31 vs 13	0.003	Obliteration or absence of the GSV: 77% vs 23% vs 85% Neovascularization: 11% vs 3% vs 44%
Samuel et al., 2013¹⁰	2004–2006	76/76	EVLA 12 W : 14 W	38:38	7 vs 0	0.27	34 vs 6	0.02
Prospective observational studies
Blomgren et al., 2004^1 3	1990–1991	100/89	HLS	–	–	–	–	–	Incompetent veins in the groin: 57%
Uema et al., 2013¹¹	–	63/39	HLS	–	–	–	–	–	Superficial venous reflux: 27% Deep venous reflux: 14% Perforator reflux: 18%
Nelzen and Fransson, 2013^1 4	1993–1998	97/93	HLS + SEPS	71^a	–	–	–	–	Groin recurrence following groin surgery: 45% (23/51) Groin recurrence following primary GSV surgery: 38% (14/37) Previously unknown deep vein incompetence: 20% (14/71), 6 had axial reflux
Merchant and Pichot, 2005^1 5	<2004	1222/1006	RFA	–	–	–	–	–	Vein occlusion: 87% Venous reflux: 16%
Proebstle et al., 2015^1 6	2006–2007	295/225	RFA	–	5	–	–	–	Complete GSV occlusion: 92%
Retrospective studies
Schnyder et al., 2012^1 7	1998–1999	136/91	GSV surgery with other concomitant surgeries	–	–	–	–	–	Nonrelevant neovascularization: 1.5%
Weiss et al., 2015^1 8	1999–2013	934/934	EVLA (810 nm) : EVLA (1320 nm) : RFA	34:502:398	–	–	–	–	Complete obliteration of the treated veins: 66% vs 85% vs 62%, p < 0.001 Recanalization: 27% vs 6.8% vs 28%

Included in analysis.

Reflux from SFJ into GSV, EVLA vs HL + EVLA: p = 0.008, EVLA vs HLS: p = 0.005.

EVLA: endovenous laser ablation; GSV: great saphenous vein; HL: high ligation; HLS: high ligation and stripping; RFA: radiofrequency thermal ablation; SEPS: subfascial endoscopic perforator surgery; SFJ: saphenofemoral junction; UGFS: ultrasound-guided foam sclerotherapy.

Studies with QoL assessment only

Results from RCTs

The UK EVLA with concomitant phlebectomy versus EVLA with sequential phlebectomy RCT¹⁹ Patients with primary symptomatic varicose veins secondary to isolated SFJ incompetence and GSV reflux were included, 21 were treated with EVLA and concomitant phlebectomy (EVLTAP), 18 were treated with EVLA with sequential phlebectomy if needed. QoL assessment. Significant improvements were observed in the SF-36 role physical domain in both groups (EVLTAP: p = 0.02; EVLA: p = 0.005), but only the EVLTAP group had significant improvements in physical functioning (p = 0.04) and bodily pain domains (p = 0.03). Significant improvements were also observed in EQ-5D in both groups following procedure and the improvements were maintained to 5 years (EVLTAP: p < 0.001; EVLA: p = 0.007). There were no statistically significant differences between the groups in SF-36 or EQ-5D. With respect to AVVQ scores, improvements following treatment were seen, in which a significant rapid decrease at 6 weeks for EVLTAP (p = 0.008) and a modest change at 12 weeks for EVLA (p = 0.02) were observed and these improvements were maintained to 5 years for both groups (p < 0.001), and the AVVQ scores were similar at 5 years (p = 0.84). Comments. Both concomitant and sequential treatment of varicose veins after EVLA are acceptable options but concomitant treatment of varicose veins is associated with optimal improvement in both clinical disease severity and QoL.

Results from prospective studies

The UK prospective study of UGFS²⁰ This patient-orientated outcome study included 391 lower limbs with truncal saphenous reflux and junctional reflux of the SFJ or saphenopopliteal junction (SPJ) treated with UGFS. During a median follow-up of 71 months, the response rate was 81%. QoL assessment. The SF-12 mental component summary scores did not change between baseline and long-term follow-up (p = 0.12), whereas the physical component summary scores was better when excluding 13 patients with recent surgery or severe illness (p = 0.02). The AVSS scores improved significantly as compared with baseline values (p < 0.001). Comments. UGFS had durable results as reported by patient-orientated outcome to at least 5 years.

Discussion

Current practice guidelines recommend duplex scanning as well as QoL assessment for follow-up of patients after treatment for chronic venous disease.^1–3 Criteria for normal and abnormal duplex exams for reflux have been well established,^1,3 but criteria of abnormal duplex findings after saphenous vein ablations are not uniform and update of reporting standards in this field is clearly warranted. There has to be a general agreement about the interpretation of abnormal duplex findings, where clinically significant axial and tributary reflux and recanalization is well established and uniform. Based on currently available duplex findings at late follow-up, four treatments including EVLA, RFA, UGFS, and traditional superficial venous surgery have been confirmed effective in the treatment of CVI. At 5 years, GSV occlusion rate on duplex ultrasound ranged from 66% to 82% for EVLA, from 62% to 92% for RFA, from 41% to 58% for UGFS, and from 54% to 85% for surgery.^8,9,15,16,18 Freedom from GSV reflux rates were 82% and 84%, respectively for EVLA and surgery,⁵ and ranged between 84% and 95% for RFA.^15,16 However, duplex-detected reflux or lack of complete ablation appear to be too sensitive and do not always correlate well with clinical recurrence or QoL data. Generic and venous disease-specific QoL instruments allow quantitative assessment of different domains of QoL, although there is a lack of consensus on which venous disease-specific QoL questionnaire is universal. Significant improvements have been observed in several domains of generic QoL and in most domains of venous disease-specific QoL irrespective of the treatment and long-term beneficial effects have been reported.^5,8–10,19 In at least one RCT, CIVIQ scores correlated very well with abnormal duplex findings in patients who underwent treatment with UGFS.⁹ In another RCT, long-term AVVQ was significantly better after surgery as compared with UGFS similar to results of duplex findings.⁸

Conclusions

Analysis of the available literature confirmed that four minimally invasive techniques (EVLA, RFA, UGFS, and modern surgery) are effective in the abolishment of reflux or obliteration of the GSV. More, well-designed RCTs with large sample size are needed to produce robust long-term data on clinical outcome after treatment of varicose veins and CVI and to better understand the relationships between duplex-derived data and QoL assessments.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

References

Gloviczki

Comerota

Dalsing

. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg 2011; 53: 2S–48S.

Wittens

Davies

Baekgaard

. Editor’s Choice - Management of chronic venous disease: Clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015; 49: 678–737.

De Maeseneer

Pichot

Cavezzi

. Duplex ultrasound investigation of the veins of the lower limbs after treatment for varicose veins - UIP consensus document. Eur J Vasc Endovasc Surg 2011; 42: 89–102.

Disselhoff

der Kinderen

Kelder

. Five-year results of a randomized clinical trial comparing endovenous laser ablation with cryostripping for great saphenous varicose veins. Br J Surg 2011; 98: 1107–1111.

Rasmussen

Lawaetz

Bjoern

. Randomized clinical trial comparing endovenous laser ablation and stripping of the great saphenous vein with clinical and duplex outcome after 5 years. J Vasc Surg 2013; 58: 421–426.

Rass

Frings

Glowacki

. Same site recurrence is more frequent after endovenous laser ablation compared with high ligation and stripping of the great saphenous vein: 5 year results of a randomized clinical trial (RELACS Study). Eur J Vasc Endovasc Surg 2015; 50: 648–656.

Kalteis

Adelsgruber

Messie-Werndl

. Five-year results of a randomized controlled trial comparing high ligation combined with endovenous laser ablation and stripping of the great saphenous vein. Dermatol Surg 2015; 41: 579–586.

Kalodiki

Lattimer

Azzam

. Long-term results of a randomized controlled trial on ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation vs standard surgery for varicose veins. J Vasc Surg 2012; 55: 451–457.

van der Velden

Biemans

De Maeseneer

. Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins. Br J Surg 2015; 102: 1184–1194.

10.

Samuel

Wallace

Carradice

. Comparison of 12-w versus 14-w endovenous laser ablation in the treatment of great saphenous varicose veins: 5-year outcomes from a randomized controlled trial. Vasc Endovasc Surg 2013; 47: 346–352.

11.

Uema

Dezotti

Joviliano

. A prospective study of venous hemodynamics and quality of live at least five years after varicose vein stripping. Acta Cir Bras 2013; 28: 794–799.

12.

Flessenkamper

Hartmann

. Endovenous laser ablation with and without high ligation compared to high ligation and stripping for treatment of great saphenous varicose veins: Results of a multicentre randomised controlled trial with up to 6 years follow-up. Phlebology 2016; 31: 23–33.

13.

Blomgren

Johansson

Dahlberg

. Recurrent varicose veins: Incidence, risk factors and groin anatomy. Eur J Vasc Endovasc Surg 2004; 27: 269–274.

14.

Nelzen

Fransson

. Varicose vein recurrence and patient satisfaction 10-14 years following combined superficial and perforator vein surgery: A prospective case study. Eur J Vasc Endovasc Surg 2013; 46: 372–377.

15.

Merchant

Pichot

. Long-term outcomes of endovenous radiofrequency obliteration of saphenous reflux as a treatment for superficial venous insufficiency. J Vasc Surg 2005; 42: 502–509; discussion 509.

16.

Proebstle

Alm

Gockeritz

. Five-year results from the prospective European multicentre cohort study on radiofrequency segmental thermal ablation for incompetent great saphenous veins. Br J Surg 2015; 102: 212–218.

17.

Schnyder

Gabler

Meier

. Successful reduction of clinical relevant neovascularization with a modified crossectomy combined with a barrier technique after 10-year follow-up. Phlebology 2012; 27: 404–408.

18.

Weiss

Eimpunth

. Comparative outcomes of different endovenous thermal ablation systems on great and small saphenous vein insufficiency: Long-term results. Lasers Surg Med 2015; 47: 156–160.

19.

El-Sheikha

Nandhra

Carradice

. Clinical outcomes and quality of life 5 years after a randomized trial of concomitant or sequential phlebectomy following endovenous laser ablation for varicose veins. Br J Surg 2014; 101: 1093–1097.

20.

Darvall

Bate

Bradbury

. Patient-reported outcomes 5-8 years after ultrasound-guided foam sclerotherapy for varicose veins. Br J Surg 2014; 101: 1098–1104.